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Of these, bcl-2 itself is an anti-apoptotic protein, which is activated by chromosomal translocations in non-Hodgkin lymphomas and is also inappropriately overexpressed in many solid tumors, contributing to resistance to chemotherapy and radiation-induced apoptosis. Unlike many other known human oncogenes, bcl-2 exerts its influence by enhancing cell survival rather than stimulating cell division.
An immunohistochemical assay for determining bcl-2 expression in archival tissues has been available for several years, and has permitted significant insight into the role of this protein in the development and progression of cancer. As an example, normal prostatic epithelium does not express bcl-2; however hormone refractory prostate cancer tissue obtained from hormone-treated patients demonstrates strong bcl-2 expression, suggesting the latter contributes to persistence of malignant cells despite the absence of a hormonal milieu. Not surprisingly, bcl-2 expression in radical prostatectomy specimens is associated higher rates of treatment failure and shorter disease free survival. In contrast, in other solid tumors such as cervical, colorectal, breast and non-small cell lung cancers, bcl-2 expression is paradoxically associated with favorable clinicopathologic parameters and a better survival. Although it may seem counterintuitive that expression of an anti-apoptotic protein would result in favorable prognosis, it is postulated that bcl-2, by virtue of inhibiting apoptosis, retards the rate of proliferation in solid tumors (i.e. cells do not die, but they do not divide either), and hence results in slow-growing tumors with a favorable outcome. It is likely that with the advent of immunohistochemical antibodies against other bcl-2 family proteins such as BAX, the complex interplay between various pro- and anti-apoptotic proteins and p53 will be better elucidated in the future.
Veripath OncoDiagnostics offers bcl-2 antibody as part of the standard gynecologic malignancy panels, but it can also be ordered individually (SEE ALSO BAX PROTEIN). Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade for bcl-2 finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Apakama I et al. Bcl-2 overexpression combined with p53 accumulation correlates with hormone refractory prostate cancer. Br J Urol 74:719; 1996
2. Joensuu H et al. Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol 145:1191; 1994
3. Le MG et al. c-myc, p53 and bcl-2, apoptosis related genes in infiltrating breast carcinomas: evidence of a link between bcl-2 protein over-expression and a lower risk of metastasis and death in operable patients. Int J Cancer 84:562; 1999
4. Manne U et al. Bcl-2 expression is associated with improved prognosis in patients with distal colorectal adenocarcinomas. Int J Cancer 89:423; 2000
5. Pezzella F et al. Bcl-2 protein in non-small cell lung carcinoma. NEJM 329:690; 1993
6. Tjalma W et al. Expression of bcl-2 in invasive and in situ carcinoma of the uterine cervix. Am J Obstet Gynecol 178:113; 1998
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